Promoting Adoption of the 3Rs through Regulatory Qualification.

One mechanism to advance the application of novel safety assessment methodologies in drug development, including in silico or in vitro approaches that reduce the use of animals in toxicology studies, is regulatory qualification. Regulatory qualification, a formal process defined at the the U. S. Food and Drug Administration and the European Medicines Agency, hinges on a central concept of stating an appropriate "context of use" for a novel drug development tool (DDT) that precisely defines how that DDT can be used to support decision making in a regulated drug development setting. When accumulating the data to support a particular "context-of-use," the concept of "fit-for-purpose" often guides assay validation, as well as the type and amount of data or evidence required to evaluate the tool. This paper will review pathways for regulatory acceptance of novel DDTs and discuss examples of safety projects considered for regulatory qualification. Key concepts to be considered when defining the evidence required to formally adopt and potentially replace animal-intensive traditional safety assessment methods using qualified DDTs are proposed. Presently, the use of qualified translational kidney safety biomarkers can refine and reduce the total numbers of animals used in drug development. We propose that the same conceptual regulatory framework will be appropriate to assess readiness of new technologies that may eventually replace whole animal models.

Evolving Global Regulatory Science Through the Voluntary Submission of Data: A 2013 Assessment.

Regulatory science, the science of developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of regulated medical products, has advanced over time due to a number of factors. The FDA, the EMA, and the Pharmaceuticals and Medical Devices Agency (PMDA) have recently formalized voluntary data submission processes for the regulatory "qualification" of novel tools and methodologies for use in drug development. While recognizing that other mechanisms exist within the research community for driving scientific consensus on novel tools and methodologies, this article focuses on the formal regulatory process that addresses a tool's acceptability for incorporation by any sponsor into novel medical product development. Guidances, regulatory qualification opinions, and publications were reviewed to allow a systematic comparison of the process, content, and volume of submissions at the FDA, EMA, and PMDA. Qualification of new tools by regulatory agencies and subsequent adoption by drug developers are anticipated to speed therapeutic development for patients in need, build scientific consensus as to the usefulness and readiness of novel methodologies for understanding disease and therapeutic development, and decrease uncertainty between the regulators and sponsors regarding the appropriate application of new tools.